Oncotarget

Research Papers:

Clinicopathological signature of p21-activated kinase 1 in prostate cancer and its regulation of proliferation and autophagy via the mTOR signaling pathway

Zhanyu Wang, Guojin Jia, Yan Li, Jikai Liu, Jinfang Luo, Jihong Zhang, Guoxiong Xu and Gang Chen _

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Oncotarget. 2017; 8:22563-22580. https://doi.org/10.18632/oncotarget.15124

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Abstract

Zhanyu Wang1, Guojin Jia1, Yan Li1, Jikai Liu1, Jinfang Luo2, Jihong Zhang3, Guoxiong Xu3,*, Gang Chen1,*

1Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China

2Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China

3Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China

*These authors contributed equally to this work

Correspondence to:

Gang Chen, email: chgan305@163.com

Guoxiong Xu, email: guoxiong.xu@fudan.edu.cn

Keywords: PAK1, prostate cancer, mTOR signaling, rapamycin, MYH1485

Received: August 02, 2016     Accepted: January 23, 2017     Published: February 06, 2017

ABSTRACT

Prostate cancer (PCa) is one of the most common malignant tumors in men. The etiology and pathogenesis of PCa remain unclear. P21-activated kinase 1 (PAK1) is a member of a family of serine/threonine kinases and regulates cell growth and contributes to tumor invasion and metastasis. However, the association of PAK1 with PCa tumorigenesis and in particular with cell autophagy remains unknown. We found that the positive expression of PAK1 was significantly increased in PCa patients compared with BPH patients (P < 0.05). The expression of PAK1, p-PAK1 and LC3B1 in DU145 was increased by the activator of mTOR MYH1485. The expression of PAK1, p-PAK1, mTOR and Beclin1 decreased in PAK1-shRNA expressing DU145 cell. Knocking down of PAK1 inhibited DU145 cell growth, invasion and migration in vitro, and inhibited tumor growth in vivo. Our study demonstrated that PAK1 is upregulated in PCa and regulated by the mTOR signaling pathway and contributes to tumor autophagy. Thus, PAK1 may be a potential tumor marker and therapeutic target of PCa.


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